The direct assessment of cellular membrane function has been enhanced by the measurement of resting transmembrane potential during hemorrhagic shock. The use of single muscle cell action potential offers further evidence for intracellular changes in response to hemorrhagic shock. When combined with direct analysis of muscle, water and electrolyte composition, extracellular (ECW) and intracellular (ICW) partition during shock and recovery can be further quantitated. It is the purpose of this proposal to extend these techniques to study calcium flux in striated skeletal muscle and the myocardium during hemorrhagic shock. In addition, the effect of pharmacologic agents on septic shock will be determined by measuring transmembrane potentials. This will allow documentation of specific defects in ion and water flux during septic shock resuscitation at the cellular level. The resting transmembrane potential will be used as an index of change in a bioassay utilizing rabbit cardic muscle. This will allow study of an active humoral factor affecting membrane permeability that is present in shock. Fluid and electrolyte shifts in human shock will be studied by the same techniques and correlated with the animal data. The end result of this entire study is to better understand shock an to apply this knowledge to the treatment of human shock.